Amino acid sequence and crystal structure of BaP1, a metalloproteinase from Bothrops asper snake venom that exerts multiple tissue-damaging activities

Autor: Jay W. Fox, Leandra Watanabe, R. David G. Theakston, Raghuvir K. Arni, José María Gutiérrez, Aura S. Kamiguti, John D. Shannon, Richard H. Valente, Alexandra Rucavado, Alberto Alape-Girón
Přispěvatelé: Univ Costa Rica, Univ Liverpool, Fiocruz MS, University of Virginia (UVA), Universidade Estadual Paulista (Unesp)
Rok vydání: 2009
Předmět:
Zdroj: Protein Science; Volumen 12, Número 10. 2003
Kérwá
Universidad de Costa Rica
instacron:UCR
Web of Science
Repositório Institucional da UNESP
Universidade Estadual Paulista (UNESP)
instacron:UNESP
ISSN: 0961-8368
Popis: Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2014-02-26T17:16:52Z No. of bitstreams: 1 WOS000185425500016.pdf: 436693 bytes, checksum: 6e53e418baab576ea898d4d9383e0c12 (MD5) Made available in DSpace on 2014-02-26T17:16:52Z (GMT). No. of bitstreams: 1 WOS000185425500016.pdf: 436693 bytes, checksum: 6e53e418baab576ea898d4d9383e0c12 (MD5) Previous issue date: 2003-10-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T14:02:23Z No. of bitstreams: 1 WOS000185425500016.pdf: 436693 bytes, checksum: 6e53e418baab576ea898d4d9383e0c12 (MD5) Made available in DSpace on 2014-05-20T14:02:24Z (GMT). No. of bitstreams: 1 WOS000185425500016.pdf: 436693 bytes, checksum: 6e53e418baab576ea898d4d9383e0c12 (MD5) Previous issue date: 2003-10-01 BaP1 is a 22.7-kD P-I-type zinc-dependent metalloproteinase isolated from the venom of the snake Bothrops asper, a medically relevant species in Central America. This enzyme exerts multiple tissue-damaging activities, including hemorrhage, myonecrosis, dermonecrosis, blistering, and edema. BaP1 is a single chain of 202 amino acids that shows highest sequence identity with metalloproteinases isolated front the venoms of snakes of the subfamily Crotalinae. It has six Cys residues involved in three disulfide bridges (Cys 117-Cys 197, Cys 159-Cys 181, Cys 157-Cys 164). It has the consensus sequence H(142)E(143)XXH(146)XXGXXH(152), as well as the sequence C164I165M166, which characterize the metzincin superfamily of metalloproteinases. The active-site cleft separates a major subdomain (residues 1-152), comprising four a-helices and a five-stranded beta-sheet, from the minor subdomain, which is formed by a single a-helix and several loops. The catalytic zinc ion is coordinated by the N-epsilon2 nitrogen atoms of His 142, His 146, and His 152, in addition to a solvent water molecule, which in turn is bound to Glu 143. Several conserved residues contribute to the formation of the hydrophobic pocket, and Met 166 serves as a hydrophobic base for the active-site groups. Sequence and structural comparisons of hemorrhagic and nonhemorrhagic P-I metalloproteinases from snake venoms revealed differences in several regions. In particular, the loop comprising residues 153 to 176 has marked structural differences between metalloproteinases with very different hemorrhagic activities. Because this region lies in close proximity to the active-site microenvironment, it may influence the interaction of these enzymes with physiologically relevant substrates in the extracellular matrix. Univ Costa Rica, Fac Microbiol, Inst Clodomiro Picado, San Jose, Costa Rica Univ Costa Rica, Escuela Med, Dept Bioquim, San Jose, Costa Rica Univ Liverpool, Royal Liverpool Univ Hosp, Dept Haematol, Liverpool, Merseyside, England Univ Liverpool, Liverpool Sch Trop Med, Venom Res Unit, Liverpool L3 5QA, Merseyside, England Fiocruz MS, Dept Fisiol & Farmacodinam, BR-21045900 Rio de Janeiro, Brazil Univ Virginia, Hlth Sci Ctr, Dept Microbiol, Charlottesville, VA 22908 USA UNESP, IBILCE, Dept Phys, BR-15054000 Sao Jose do Rio Preto, Brazil UNESP, IBILCE, Dept Phys, BR-15054000 Sao Jose do Rio Preto, Brazil
Databáze: OpenAIRE
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